Receiving a large, multi-year research award is an honor for any scientist, but receiving two grants within a month’s time is truly an exceptional accomplishment. This fall, Laura E. Nagy, PhD, Pathobiology Staff and Director of Lerner Research Institute’s Center for Liver Disease Research, received two U01 grants from the National Institute on Alcohol Abuse and Alcoholism/National Institutes of Health (NIAAA/NIH).
The first grant is a 5-year, $2.1M U01 titled “Migration inhibitory factor in progression and treatment of alcoholic liver disease.” With this grant, Dr. Nagy will examine whether genetic variation in a specific protein—migration inhibitory factor—can predict the incidence and/or severity of alcoholic liver disease (ALD). Ninety percent of alcoholics develop fatty liver, and a subset of that population progresses to the more serious ALD. Dr. Nagy’s team will collaborate with groups in Italy and Spain to examine genetic variation in patients with ALD. They will examine samples taken from the entire population of two Italian villages almost 30 years ago, allowing them to observe how ALD has progressed over time.
Dr. Nagy’s second award is a 5-year, $1.4M U01 for “Novel therapeutics for alcoholic hepatitis - Cleveland translational component.” In this large, multi-institutional study, Dr. Nagy will search for potential new drug targets for alcoholic hepatitis (AH), one of the most serious forms of alcohol-induced liver disease. She will focus her efforts on the role of gut integrity and inflammation in the development of the disease. Arthur McCullough, MD, Gastroenterology and Hepatology, will lead a clinical trial component of the grant, from which Dr. Nagy will obtain human samples for her studies. For the clinical trial, Dr. McCullough and his consortium of investigators at University of Massachusetts, University of Louisville, and University of Texas Southwest will receive $5.5M over five years. AH has a high short-term mortality rate, and those who do survive have a 70 percent probability of developing cirrhosis.
Matt Hiznay is a bright, energetic first-year graduate student working toward a PhD in Molecular Medicine. He also happens to have stage IV lung cancer.
After a nagging cough and lump in his shoulder sent him to his family doctor last summer, Matt received an unbelievable diagnosis—anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC). Not only did he have cancer at age 25, but he had a rare, aggressive one that had spread to both lungs and lymph nodes in his chest and near his stomach. At the time, Matt was a medical student at the University of Toledo College of Medicine, so he understood all too well the gravity of his diagnosis.
ALK-positive NSCLC—found predominantly in young nonsmokers—is caused by a genetic mutation that leads to an inversion in chromosome 2. That inversion causes ALK to fuse with another protein, EML4. The presence of the abnormal, fused protein causes cancer in otherwise healthy individuals. Ironically (some might say miraculously), the same day that Matt received his diagnosis, the U.S. Food and Drug Administration approved a chemotherapy drug, Xalkori, to specifically treat patients who carry the abnormal ALK gene.
Matt was treated by Nathan Pennell, MD, PhD, Solid Tumor Oncology. While he was at Cleveland Clinic for a pretreatment checkup, a massive buildup of fluid around his heart and lungs caused his heart to stop. A team of ICU surgeons performed emergency surgery to drain the fluid, saving Matt’s life. After recovering from that near-death experience, Matt began treatment with Xalkori, and, amazingly, his cancer was in remission within a few months’ time.
Despite his progress, Matt decided to leave medical school because it had become physically challenging for him to visit with patients. He decided to pursue a career in biomedical research.
Matt says he always had a love for research; he had done undergraduate work at John Carroll University and worked as a summer student in the lab of Kathy Berkner, PhD, Molecular Cardiology. “Even if I would have become a doctor, I still would have done research,” he explains. Hoping to pursue that interest at Cleveland Clinic, Matt contacted another John Carroll alumna, Christine Moravec, PhD, Cardiovascular Medicine, to inquire about Cleveland Clinic’s Molecular Medicine (MMED) PhD program. MMED is a unique program that integrates medicine with traditional graduate training in biomedical research—so it seemed like a great fit.
By the time Matt contacted Dr. Moravec, the MMED program had already begun a few weeks earlier. Dr. Moravec contacted the program leadership to inquire about the possibility of late admission to the program. Matt was invited to apply and he entered the rigorous MMED admissions process.
Matt’s highly competitive application was reviewed and he was accepted into the program. He quickly acclimated to graduate studies and became very close with his classmates: “Even though this is a very competitive field, they welcomed me with open arms,” he says. He enjoys the small group setting of the MMED classes, especially in contrast to medical school. Rather than attending class with 150 students in a lecture hall, his class here consists of nine students who sit around a table and have an open, fluid discussion with their professor.
Matt is currently in his first research rotation in the lab of Raed Dweik, MD, Pathobiology, where he studies pulmonary hypertension, with hopes that the research might someday benefit breath analysis studies in patients with lung diseases.
Matt has had some setbacks with his illness and, unfortunately, is no longer in remission. He travels frequently to receive treatment but remains engaged with his school work and optimistic for the future. He says, “I tell people, don’t let things get you down. If your experiments aren’t working, don’t panic, just try again. You have many chances to make things work in the lab, but only one chance at life.”
Despite the explosion of biological knowledge that has occurred in the past 10 years, new treatments have simply not kept up with our understanding of science. Researchers have made tremendous progress in understanding the mechanisms that underlie many diseases, yet few of those have led to new drugs on the market. Why is there a disconnect between the laboratory and potential cures?
Pat Fortune, PhD, MBA, Innovations Senior General Manager, believes part of the problem lies in a lack of effective communication between scientists, clinicians, and pharmaceutical companies. He describes the current pharmaceutical climate as “dismal,” and believes collaboration will facilitate more discoveries that lead to effective treatments.
Dr. Fortune joined Cleveland Clinic in May, after serving on its industrial advisory board for seven years. With a PhD in physical chemistry from the University of Wisconsin-Madison and MBA from Northwestern University, he has spent over 30 years as a business leader in the health care industry and the past 11 years at Boston Millennia Partners, a venture capital firm specializing in emerging business in healthcare services, healthcare IT, and life sciences.
Dr. Fortune was attracted to Cleveland Clinic because of its culture of innovation. “It’s a pretty exciting time in healthcare,” he explains. “Cleveland Clinic will be at the epicenter of where some of the changes get developed, implemented, demonstrated, and then delivered to the rest of the world.”
Dr. Fortune works closely with LRI researchers to help them identify early-stage projects that will result in actionable intellectual property. He is meeting with individual departments and is available for consultation with any LRI researcher who is interested in learning about the commercialization potential of their work.
“We expect Pat will be a great partner to LRI,” said Paul E. DiCorleto, PhD, LRI’s Sherwin-Page Chair. His active engagement of Staff, coupled with an exceptionally broad network in the pharmaceutical and investment communities, should accelerate the movement of LRI discoveries to commercial application.”
Dr. Fortune hopes to promote the unique capabilities and resources at Cleveland Clinic and LRI to the pharmaceutical industry. He touts our close proximity of first-rate clinical research, basic research, and clinical delivery and describes LRI as a unique incubator for the discovery of therapeutics. By investing in academic research centers like LRI to perform early-stage drug discovery and candidate screening, Dr. Fortune explains, pharmaceutical companies can improve their chances of success and reduce the billions of dollars they spend every year on failed drug trials.
These partnerships will not only expedite the commercialization of scientific discoveries, but could potentially improve quality of life and affordability of health care for all.